Show simple item record

dc.contributor.authorHuang, Bin
Lu, Mingyang
Jia, Dongya
Ben-Jacob, Eshel
Levine, Herbert
Onuchic, José N.
dc.date.accessioned 2017-05-05T19:00:53Z
dc.date.available 2017-05-05T19:00:53Z
dc.date.issued 2017
dc.identifier.citation Huang, Bin, Lu, Mingyang, Jia, Dongya, et al.. "Interrogating the topological robustness of gene regulatory circuits by randomization." PLoS Computational Biology, 13, no. 3 (2017) Public Library of Science: https://doi.org/10.1371/journal.pcbi.1005456.
dc.identifier.urihttps://hdl.handle.net/1911/94196
dc.description.abstract One of the most important roles of cells is performing their cellular tasks properly for survival. Cells usually achieve robust functionality, for example, cell-fate decision-making and signal transduction, through multiple layers of regulation involving many genes. Despite the combinatorial complexity of gene regulation, its quantitative behavior has been typically studied on the basis of experimentally verified core gene regulatory circuitry, composed of a small set of important elements. It is still unclear how such a core circuit operates in the presence of many other regulatory molecules and in a crowded and noisy cellular environment. Here we report a new computational method, named random circuit perturbation (RACIPE), for interrogating the robust dynamical behavior of a gene regulatory circuit even without accurate measurements of circuit kinetic parameters. RACIPE generates an ensemble of random kinetic models corresponding to a fixed circuit topology, and utilizes statistical tools to identify generic properties of the circuit. By applying RACIPE to simple toggle-switch-like motifs, we observed that the stable states of all models converge to experimentally observed gene state clusters even when the parameters are strongly perturbed. RACIPE was further applied to a proposed 22-gene network of the Epithelial-to-Mesenchymal Transition (EMT), from which we identified four experimentally observed gene states, including the states that are associated with two different types of hybrid Epithelial/Mesenchymal phenotypes. Our results suggest that dynamics of a gene circuit is mainly determined by its topology, not by detailed circuit parameters. Our work provides a theoretical foundation for circuit-based systems biology modeling. We anticipate RACIPE to be a powerful tool to predict and decode circuit design principles in an unbiased manner, and to quantitatively evaluate the robustness and heterogeneity of gene expression.
dc.language.iso eng
dc.publisher Public Library of Science
dc.rights This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.title Interrogating the topological robustness of gene regulatory circuits by randomization
dc.type Journal article
dc.citation.journalTitle PLoS Computational Biology
dc.contributor.org Center for Theoretical Biological Physics
dc.citation.volumeNumber 13
dc.citation.issueNumber 3
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1371/journal.pcbi.1005456
dc.identifier.pmcid PMC5391964
dc.identifier.pmid 28362798
dc.type.publication publisher version
dc.citation.articleNumber e1005456


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.